The present invention relates to a process for the purification of pharmaceutical grade 1,1,1,2-tetrafluoroethane (HFC-134a) and for the purification of chlorodifluoromethane (HCFC-22) by the removal of impurities including methyl chloride.
Delivery of drugs to the lung by way of inhalation is an important means of treating a variety of conditions, including such common local conditions as cystic fibrosis, pneumonia, bronchial asthma and chronic obstructive pulmonary disease and some systemic conditions including pain management, immune deficiency, hormonal therapy, erythropoiesis, diabetes, etc. Such drugs are commonly administered to the lung as an aerosol of respirable size particles (less than about 10 μm in diameter). In order to assure proper particle size in the aerosol, particles can be prepared in respirable size and then incorporated into a colloidal dispersion containing a propellant, as a pressurized metered dose inhaler (MDI). Solutions of formulations must be dispensed in a manner that produces particles or droplets of respirable size. For MDI applications, a prepared aerosol formulation is filled into an aerosol canister equipped with a metered dose valve. The formulation is dispensed via an actuator adapted to direct the dose from the valve to the patient. Metered dose aerosol canisters deliver the medicine to be inhaled into the mouth, nasal areas or respiratory airways. Examples of metered dose inhalers are set forth in U.S. Pat. Nos. 5,544,647; 5,622,163 and 6,581,590.
HFC-134a is an environmentally acceptable potential replacement for chlorofluorocarbon refrigerants, blowing agents, aerosol propellants and sterilants that are being viewed with concern in connection with the destruction of stratospheric ozone. HFC-134a has been known as a propellant for a metered dose inhaler for pharmaceutical compositions. Pharmaceutical compositions comprising a pharmaceutically active agent in 1,1,1,2-tetrafluoroethane (HFC-134a) as a propellant, for delivery in aerosol form, and to a device for delivering such a composition as an aerosol are known from U.S. Pat. No. 6,413,496. The use of HFC-134a in such pharmaceutical applications requires that it be of extremely high purity, i.e. significantly more pure than that which would be more typically used in refrigeration. In meeting the specifications for pharmaceutical use, a key impurity to be removed is methyl chloride. The manufacture of pharmaceutical grade HFC-134a has been a problem since the desired pharmaceutical use makes purification by traditional distillation techniques difficult due to the presence of close boiling point methyl chloride impurities. This is because HFC-134a and methyl chloride differ in normal boiling point by only 3° C. This small difference in boiling point requires high reflux ratios in order to achieve separation. This process is extremely energy intensive and reduces the throughput capability of the manufacturing system. An improvement over the known methods to ensure a cost effective process would be desired.
HCFC-22 is a refrigerant which is useful for the production of tetrafluoroethylene monomer which is a precursor for the production of polytetrafluoroethylene (Teflon).
The inventive improvement provides a technique for removing methyl chloride from HFC-134a or HCFC-22 by contacting a mixture of methyl chloride and HFC-134a or HCFC-22 with a molecular sieve. This technique may also be used to remove methyl chloride and other impurities from a variety of halocarbons where separation by distillation or other means is impractical or inefficient. The use of molecular sieve for this separation substantially reduces energy requirements and does not show a reduction in throughput for the purification process. This results in a more cost effective alternative to conventional distillation techniques.